Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer.
The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement.
TMPRSS2-ERG is a recurrent rearrangement specific for prostate cancer, leading to the overexpression of a truncated ERG protein product that is amenable to immunohistochemical detection.
The transmembrane protease, serine 2:ets-related gene (TMPRSS2:ERG) gene fusion leads to the overexpression of ERG, an E-twenty six (ETS) family transcription factor, and is the most prevalent genetic lesion in prostate cancer, but its clinical utility remains unclear.
These results demonstrate that TMPRSS2:ERG gene fusions can be detected in the urine of patients with prostate cancer and support larger studies on prospective cohorts for noninvasive detection of prostate cancer.
Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reverse-transcriptase polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERG fusion transcripts.
A major breakthrough in prostate cancer was the identification of recurrent fusions between the androgen-regulated gene, TMPRSS2 and the v-ets erythroblastosis virus E26 oncogene homolog, ERG.
The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer.
The significant associations with key genomic alterations of prostate cancer, such as TMPRSS2:ERG fusions and PTEN deletions, suggest interactions with several pivotal pathways involved in prostate cancer.
The majority of human PCas express a transmembrane protease serine 2 (TMPRSS2):erythroblast transformation-specific (ETS) fusion gene, but most preclinical studies have been performed in PCa models lacking TMPRSS2:ETS in part due to the limited availability of model systems expressing endogenous TMPRSS2:ETS.
These findings suggest that TMPRSS2-ERG with Edel is an aggressive and, in this study, uniformly lethal molecular subtype of prostate cancer associated with androgen-independent disease.
We therefore designed and optimized a pipeline involving target capture of TMPRSS2 and ERG genomic sequences coupled with paired-end next-generation sequencing to resolve genomic rearrangement breakpoints in TMPRSS2 and ERG at nucleotide resolution in a large series of primary prostate cancer specimens (n = 83).
Furthermore, our data indicated that CTS could modulate AR transactivation and suppress the DHT-mediated AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive PCa LNCaP cells and castration resistant CWR22rv1 cells.
SLC45A3-ERG and TMPRSS2-ERG rearrangements and their association with ERG and PTEN expression and with clinical and pathological features have been analyzed in 80 PrCa (PSMAR-Biobank, Barcelona, Spain).
However, due to the high specificity, TMPRSS2: ERG detection maybe can serve as a quick and noninvasive method for confirming prostate cancer diagnosis.
This combination was most effective in the presence of the TMPRSS2-ERG and in the absence of PTEN, indicating clinical potential for brachytherapy in patients with intermediate and high risk PCa.